Medincell announced that the Phase 3 trial for F14 (mdc-CWM) being conducted by Arthritis Innovation Corporation (AIC) did not meet its primary endpoint of time-weighted AUC1 of pain intensity over 14 dayswhen comparing treatment with multimodal analgesia (MMA) alone to MMA concurrent with a single dose of F14 administered in the knee at the time of Total Knee Replacement (TKR). The MMA control analgesia that every patient received was defined by the protocol as standard of care periarticular infiltration with bupivacaine, oral acetaminophen and opioid rescue medication. A numerical improvement favoring F14 was observed for the primary endpoint.Secondary endpoints of time-weighted AUC of pain over 3 and 7 days also demonstrated numerical improvement favoring F14.

The safety profile for F14 was consistent with the prior Phase 2 study, and no new safety signals were identified, and no SAEs2 were reported as related to F14 treatment. Based on Medincell?s BEPO® technology, F14 represents a novel sustained-release, non-steroidal anti-inflammatory drug (NSAID) for intra-articular, targeted delivery. Thus, this study also investigated multiple outcomes related to inflammation (and not simply pain) following TKR.

Substantial improvement was observed for F14-treated patients for the key secondary endpoint of knee range of motion (ROM) at 6 weeks, as well as at 3 months (p<0.005 and p<0.0005 respectively; unadjusted for multiplicity). Treated-knee effusion (i.e., swelling) showed highly improved outcomes for the F14-treated patients compared to MMA at 6 weeks and 3 months (p<0.005 and p<0.05 respectively, unadjusted for multiplicity). The widely used clinical-performance based measure of lower extremity function, the Timed-Up-and-Go (TUG) test was also improved for the F14 group at 6 weeks.

Notably, far greater improvements were observed for the endpoints of time-weighted AUC of pain, ROM, effusion, and TUG in a sub-group of patients representing over 70% of the trial population (108/151) who had not previously undergone TKR in their contralateral (non-study) knee. This subset analysis was pre-specified in the protocol, but not alpha-controlled for formal statistical testing. AIC intends to discuss the results from this trial with regulators and explore alternative approval pathways for F14 in this sub-group of patients.